Key result
Serum ACTC1 mRNA accurately detects acute cellular rejection grade ≥2R with an AUC of ~1.0.
Why the study?
Given the role of sarcomeric dysfunction in rejection, this study aimed to identify altered sarcomere-related molecules in serum and evaluate their diagnostic accuracy for acute cellular rejection.
Does serum alpha-cardiac actin expression accurately detect acute cellular rejection in heart transplant patients?
Observational (n=120)
Blinded to group allocation and outcome assessment
No
Does serum alpha-cardiac actin expression accurately detect acute cellular rejection in heart transplant patients?
Serum alpha-cardiac actin levels show significant diagnostic capacity and may serve as a noninvasive biomarker for detecting acute cellular rejection in heart transplant recipients.
May aid noninvasive rejection surveillance post-transplant; hypothesis-generating and requires prospective validation before clinical adoption.
BACKGROUND: Given the central role of sarcomeric dysfunction in cardiomyocyte biology and sarcomere alterations described in endomyocardial biopsies of transplant patients with rejection, we hypothesized that the serum expression levels of genes encoding sarcomeric proteins were altered in acute cellular rejection (ACR). The aim of this study is to identify altered sarcomere-related molecules in serum and to evaluate their diagnostic accuracy for detecting rejection episodes. METHODS: Serum samples from transplant recipients undergoing routine endomyocardial biopsies were included in an RNA sequencing analysis (n = 40). Protein concentrations of alpha-cardiac actin were determined using a specific enzyme-linked immunoassay (n = 80). RESULTS: We identified 17 sarcomeric genes differentially expressed in patients with clinically relevant rejection (grade ≥2R ACR). A receiver operating characteristic curve was done to assess their accuracy for ACR detection and found that 6 relevant actins, myosins, and other sarcomere-related genes showed great diagnostic capacity with an area under the curve (AUC) > 0.800. Specifically, the gene encoding alpha-cardiac actin ( ACTC1 ) showed the best results (AUC = 1.000, P < 0.0001). We determine ACTC1 protein levels in a larger patient cohort, corroborating its overexpression and obtaining a significant diagnostic capacity for clinically relevant rejection (AUC = 0.702, P < 0.05). CONCLUSIONS: Sarcomeric alterations are reflected in peripheral blood of patients with allograft rejection. Because of their precision to detect ACR, we propose sarcomere ACTC1 serum expression levels as potential candidate for to be included in the development of molecular panel testing for noninvasive ACR detection.
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Pérez-Carrillo et al. (2022) conducted an observational in Acute Cellular Rejection (n=120). Serum alpha-cardiac actin (ACTC1) expression levels vs. Patients without clinically relevant rejection (grade <2R ACR) was evaluated on Diagnostic accuracy (Area Under the Curve) of ACTC1 mRNA levels for detecting acute cellular rejection grade ≥2R (AUC 1.000, 95% CI 1.000-1.000, p=<0.0001). Serum ACTC1 mRNA and protein levels demonstrated high diagnostic capacity for detecting clinically relevant acute cellular rejection (grade ≥2R), achieving an AUC of 1.000 and 0.702 respectively.
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